Oxidant-induced increase in vascular permeability is inhibited by oral administration of S-5682 (Daflon 500 mg) and alpha-tocopherol.
The aim was to study the effect of oral administration of three different doses of S-5682 and alpha-tocopherol on an oxidant-induced injury by tert-butylhydroperoxide (TBOOH) resulting in increased plasma leakage from postcapillary venules in the hamster cheek pouch microcirculation. Hamsters were on a standard laboratory animal diet with normal vitamin E and C content. Five groups of hamsters (n = 6) were treated orally with placebo (10% lactose solution), S-5682 (5, 20 or 80 mg/kg/day) suspended in 10% lactose solution, or alpha-tocopherol (1 mg/kg/day) for 10 days prior to oxidant challenge with TBOOH. Topical application of 10(-4) M TBOOH for 5 min to hamsters given FITC-dextran 30 min prior to TBOOH resulted in reversible increases in the number (mean +/- SE) of leaks in postcapillary venules: placebo, 117+/-7 leaks/cm2; S-5682, 5 mg/kg/day, 68+/-3 leaks/cm2 (p < 0.01); S-5682, 20 mg/kg/day, 41+/-3 leaks/cm2 (p < 0.01); S-5682, 80 mg/kg/day, 25+/-2 leaks/cm2 (p < 0.001), and alpha-tocopherol, 1 mg/kg/day, 18+/-1 leaks/cm2 (p < 0.001). The efficacy of inhibition of oxidant-induced leakage by S-5682 was similar to that seen with the same dose (20 mg/kg/day) of histamine, bradykinin, leukotriene B4 or ischemia/reperfusion-induced leakage, suggesting a common pathway for the induction of plasma leakage by these mediators. The maximal dose of S-5682 (80 mg/kg/day) was as effective as alpha-tocopherol (1 mg/kg/day) in inhibiting plasma leakage.
Bouskela
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E
Laboratório de Pesquisas em Microcirculação, Universidade do Estado do Rio de Janeiro, Brasil.
Svensjö
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E
Cyrino
F Z
FZ
Lerond
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L
D000284:Administration, Oral; D000818:Animals; D019559:Capillary Leak Syndrome / Q000188:drug therapy*; D002199:Capillary Permeability / Q000187:drug effects*; D006224:Cricetinae; D004145:Diosmin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008647:Mesocricetus; D010545:Peroxides / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species; D014810:Vitamin E / Q000627:therapeutic use*; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D017382:Reactive Oxygen Species; D014810:Vitamin E; D004145:Diosmin; D020122:tert-Butylhydroperoxide